Integrating ancillary studies in a large clinical trial: The design and rationale of the APEX library

Copyright © 2008 Elsevier B.V. All rights reserved. ScienceDirect® is a registered trademark of Elsevier B.V.The APEX library was a coordinated and integrated set of ancillary analyses and substudies that were a part of the large APEX-AMI trial. The library included electrocardiogram, angiographic, blood biomarker, genetics, and MRI components. Operationally, the goals and administration of the APEX library were developed concurrently with the design of the parent trial. The goal recruitment in the library was met due to this approach. These data will provide important insights into the pathobiology of acute myocardial infarction and the relationships between inflammation, thrombosis, genetics, and classic clinical markers from angiograms, electrocardiograms, and patient demographics. In conclusion, the APEX library is an example of successful collaboration among academic trial leaders, site investigators, and pharmaceutical sponsors. The operational paradigm of this effort should be considered in future investigations so that important advances in clinical care of disease can be realized efficiently.Kenneth W. Mahaffey, Craig J. Reist, Yuling Fu, Sorin J. Brener, Pierre Theroux, Manesh R. Patel, Amanda Stebbins, Cynthia M. Westerhout, Thomas G. Todaro, Peter X. Adams, Christopher B. Granger, Paul W. Armstrong, on behalf of the APEX Library Study Investigator

Self-Regulated Pax Gene Expression and Modulation by the TGFβ Superfamily

The mammalian Pax gene family encode a set of paired-domain transcription factors which play essential roles in regulating proliferation, differentiation, apoptosis, cell migration, and stem-cell maintenance. Pax gene expression is necessarily tightly controlled and is associated with the demarcation of boundaries during tissue development and specification. Auto- and inter-regulation are mechanisms frequently employed to achieve precise control of Pax expression domains in a variety of tissues including the eye, central nervous system, kidney, pancreas, skeletal system, muscle, tooth, and thymus. Furthermore, aberrant Pax expression is linked to several diseases and causally associated with certain tumors. An increasing number of studies also relate patterns of Pax expression to signaling by members of the TGFß superfamily and, in some instances, this is due to disruption of Pax gene auto-regulation. Here, we review the current evidence highlighting functional and mechanistic overlap between TGFß signaling and Pax-mediated gene transcription. We conclude that self-regulation of Pax gene expression coupled with modulation by the TGFß superfamily represents a signaling axis that is frequently employed during development and disease to drive normal tissue growth, differentiation and homeostasis